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Berberine Promotes Glucose Consumption Independently of AMP-Activated Protein Kinase Activation
- Source :
- PLoS ONE, Vol 9, Iss 7, p e103702 (2014), PLoS ONE
- Publication Year :
- 2014
- Publisher :
- Public Library of Science (PLoS), 2014.
-
Abstract
- Berberine is a plant alkaloid with anti-diabetic action. Activation of AMP-activated protein kinase (AMPK) pathway has been proposed as mechanism for berberine's action. This study aimed to examine whether AMPK activation was necessary for berberine's glucose-lowering effect. We found that in HepG2 hepatocytes and C2C12 myotubes, berberine significantly increased glucose consumption and lactate release in a dose-dependent manner. AMPK and acetyl coenzyme A synthetase (ACC) phosphorylation were stimulated by 20 µmol/L berberine. Nevertheless, berberine was still effective on stimulating glucose utilization and lactate production, when the AMPK activation was blocked by (1) inhibition of AMPK activity by Compound C, (2) suppression of AMPKα expression by siRNA, and (3) blockade of AMPK pathway by adenoviruses containing dominant-negative forms of AMPKα1/α2. To test the effect of berberine on oxygen consumption, extracellular flux analysis was performed in Seahorse XF24 analyzer. The activity of respiratory chain complex I was almost fully blocked in C2C12 myotubes by berberine. Metformin, as a positive control, showed similar effects as berberine. These results suggest that berberine and metformin promote glucose metabolism by stimulating glycolysis, which probably results from inhibition of mitochondrial respiratory chain complex I, independent of AMPK activation.
- Subjects :
- Adenoviruses
Berberine
lcsh:Medicine
AMP-Activated Protein Kinases
Mitochondrion
Biochemistry
Mice
chemistry.chemical_compound
RNA interference
Endocrinology
Adenosine Triphosphate
Cell Signaling
AMP-activated protein kinase
Molecular Cell Biology
Drug Discovery
Medicine and Health Sciences
Mitochondrial respiratory chain complex I
Glycolysis
Phosphorylation
RNA, Small Interfering
lcsh:Science
Multidisciplinary
Protein Kinase Signaling Cascade
biology
Hep G2 Cells
Signaling Cascades
Type 2 Diabetes
Viruses
Carbohydrate Metabolism
Epigenetics
Research Article
Signal Transduction
Drug Research and Development
Acetate-CoA Ligase
Adenoviridae
Cell Line, Tumor
Genetics
Diabetes Mellitus
Animals
Humans
Hypoglycemic Agents
Lactic Acid
Protein kinase A
Diabetic Endocrinology
Pharmacology
Electron Transport Complex I
Biology and life sciences
lcsh:R
Organisms
AMPK
Cell Biology
Metabolism
Glucose
Amino Acid Substitution
chemistry
Metabolic Disorders
biology.protein
lcsh:Q
DNA viruses
Subjects
Details
- ISSN :
- 19326203
- Volume :
- 9
- Database :
- OpenAIRE
- Journal :
- PLoS ONE
- Accession number :
- edsair.doi.dedup.....46ac2d0d90a9442ccdfd8fbc6abd2a6c